Our findings shed light on the molecular mechanism underlying the expression of PERK and indicate that RHBDF1 plays a substantial role in supporting the UPR not only by stabilizing BiP[22] but also by regulating the PERK/peIF2α pathway, which may be one of the main mechanisms by which RHBDF1 promotes breast cancer development and chemotherapy resistance. The gene discussed is EIF2AK3; the disease is breast cancer.